Constitutional risk factors for focal neuropathies in patients referred for electromyography.

BACKGROUND AND PURPOSE: It is well established that patient-related constitutional features predispose to focal peripheral neuropathies. Some of these risk factors were investigated in common focal neuropathies encountered in patients referred for electromyography. METHODS: Gender, age, height and body mass index (BMI) were analysed retrospectively as risk factors for 11 focal neuropathies. In all, 9686 patients (age range 18-96 years; 58% women) were included from three different centres, with identical methods and equipment. RESULTS: High BMI was related to carpal tunnel syndrome (CTS), ulnar neuropathy at the elbow (UNE), combined CTS and UNE, meralgia paraesthetica and lumbar radiculopathy. In women, CTS and Morton's metatarsalgia were more common, whilst long thoracic neuropathies, suprascapular neuropathies and UNE were more common in men. Older age increased the risk for CTS, UNE, Morton's metatarsalgia and radiculopathies. CONCLUSIONS: Age, gender and BMI are important risk factors for many common focal neuropathies.

Peripheral nervous system involvement in primary burning mouth syndrome--results of a pilot study.

OBJECTIVE: The pathophysiology of primary burning mouth syndrome (BMS) has remained enigmatic, but recent studies suggest pathology within the nervous system at multiple levels. This study aimed to investigate in detail the contribution of either focal or generalized alterations within the peripheral nervous system (PNS) in the etiopathogenesis of BMS. SUBJECTS AND METHODS: Intraepithelial nerve fiber density (IENFD) of tongue mucosa was assessed in 10 carefully characterized BMS, and the results were compared to 19 age- and gender-matched cadaver controls, 6 with lifetime diabetes. Extensive neurophysiologic and psychophysical examinations of the trigeminal system and distal extremities were performed to profile PNS function in BMS. RESULTS: Patients with BMS had significantly fewer intraepithelial nerve fibers (0,27, s.e. 0,18 mm(-1); P = 0.0253) than non-diabetic controls (0,92, s.e. 0,15 mm(-1)). In the subepithelial space, the amount of nerve fibers did not differ between the groups. The majority (9/10) of patients with BMS showed neurophysiologic or psychophysical signs of a more generalized PNS dysfunction. CONCLUSIONS: Our results in neurophysiologically optimally characterized BMS patients confirm that pure focal small fiber neuropathy of the oral mucosa has a role in the pathophysiology of primary BMS. Furthermore, BMS may be related to a more generalized, yet subclinical peripheral neuropathy.

Pathophysiology of primary burning mouth syndrome with special focus on taste dysfunction: a review.

Primary burning mouth syndrome (BMS) is a chronic oral condition characterized by burning pain often accompanied with taste dysfunction and xerostomia. The most compelling evidence concerning BMS pathophysiology comes from studies on the somatosensory system using neurophysiologic or psychophysical methods such as blink reflex, thermal quantitative sensory testing, as well as functional brain imaging. They have provided convincing evidence for neuropathic involvement at several levels of the somatosensory system in BMS pain pathophysiology. The number of taste function studies trying to substantiate the subjective taste disturbances or studies on salivary factors in BMS is much more limited, and most of them suffer from definitional and methodological problems. This review aims to critically evaluate the existing literature on the pathophysiology of BMS, paying special attention to the correctness of case selection and the methodology used in published studies, and to summarize the current state of knowledge. Based on the recognition of several gaps in the current understanding of the pathophysiology of BMS especially as regards taste and pain system interactions, the review ends with future scenarios for research in this area.

Electroencephalogram reactivity to verbal command after dexmedetomidine, propofol and sevoflurane-induced unresponsiveness.

Although electroencephalogram reactivity (i.e. transient changes in electrical brain activity following external stimulus) might be useful in depth-of-anaesthesia monitoring, it has not been systematically examined with different anaesthetics at doses titrated to unresponsiveness. Three 10-subject groups of healthy volunteers received dexmedetomidine, propofol or sevoflurane in escalating pseudo-steady-state concentrations at 10-min intervals until they did not open their eyes to command. The electroencephalogram was continuously recorded and spectral variables were calculated with short-time Fourier transform and time-varying autoregressive modelling. Electroencephalogram reactivity was most prominent in the midfrontal derivations (termed F3 and F4). During drug-induced unresponsiveness, electroencephalogram reactivity was still present in all drug groups. Dexmedetomidine, propofol and sevoflurane induced distinct suppression patterns on the electroencephalogram reactivity at the same clinical endpoint (unresponsiveness). Reactivity was best maintained with propofol, while only minimally preserved with dexmedetomidine and sevoflurane. Thus, it may be difficult to harness reactivity for depth-of-anaesthesia monitoring.

Guidelines and recommendations for assessment of somatosensory function in oro-facial pain conditions--a taskforce report.

The goals of an international taskforce on somatosensory testing established by the Special Interest Group of Oro-facial Pain (SIG-OFP) under the International Association for the Study of Pain (IASP) were to (i) review the literature concerning assessment of somatosensory function in the oro-facial region in terms of techniques and test performance, (ii) provide guidelines for comprehensive and screening examination procedures, and (iii) give recommendations for future development of somatosensory testing specifically in the oro-facial region. Numerous qualitative and quantitative psychophysical techniques have been proposed and used in the description of oro-facial somatosensory function. The selection of technique includes time considerations because the most reliable and accurate methods require multiple repetitions of stimuli. Multiple-stimulus modalities (mechanical, thermal, electrical, chemical) have been applied to study oro-facial somatosensory function. A battery of different test stimuli is needed to obtain comprehensive information about the functional integrity of the various types of afferent nerve fibres. Based on the available literature, the German Neuropathic Pain Network test battery appears suitable for the study of somatosensory function within the oro-facial area as it is based on a wide variety of both qualitative and quantitative assessments of all cutaneous somatosensory modalities. Furthermore, these protocols have been thoroughly described and tested on multiple sites including the facial skin and intra-oral mucosa. Standardisation of both comprehensive and screening examination techniques is likely to improve the diagnostic accuracy and facilitate the understanding of neural mechanisms and somatosensory changes in different oro-facial pain conditions and may help to guide management.

Neurotransmitters behind pain relief with transcranial magnetic stimulation - positron emission tomography evidence for release of endogenous opioids.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) at M1/S1 cortex has been shown to alleviate neuropathic pain. OBJECTIVES: To investigate the possible neurobiological correlates of cortical neurostimulation for the pain relief. METHODS: We studied the effects of M1/S1 rTMS on nociception, brain dopamine D2 and µ-opioid receptors using a randomized, sham-controlled, double-blinded crossover study design and 3D-positron emission tomography (PET). Ten healthy subjects underwent active and sham rTMS treatments to the right M1/S1 cortex with E-field navigated device. Dopamine D2 and µ-receptor availabilities were assessed with PET radiotracers [11 C]raclopride and [11 C]carfentanil after each rTMS treatment. Thermal quantitative sensory testing (QST), contact heat evoked potential (CHEP) and blink reflex (BR) recordings were performed between the PET scans. RESULTS: µ-Opioid receptor availability was lower after active than sham rTMS (P ≤ 0.0001) suggested release of endogenous opioids in the right ventral striatum, medial orbitofrontal, prefrontal and anterior cingulate cortices, and left insula, superior temporal gyrus, dorsolateral prefrontal cortex and precentral gyrus. There were no differences in striatal dopamine D2 receptor availability between active and sham rTMS, consistent with lack of long-lasting measurable dopamine release. Active rTMS potentiated the dopamine-regulated habituation of the BR compared to sham (P = 0.02). Thermal QST and CHEP remained unchanged after active rTMS. CONCLUSIONS: rTMS given to M1/S1 activates the endogenous opioid system in a wide brain network associated with processing of pain and other salient stimuli. Direct enhancement of top-down opioid-mediated inhibition may partly explain the clinical analgesic effects of rTMS. SIGNIFICANCE: Neurobiological correlates of rTMS for the pain relief are unclear. rTMS on M1/S1 with 11 C-carfentanyl-PET activates endogenous opioids. Thermal and heat pain thresholds remain unchanged. rTMS induces top-down opioid-mediated inhibition but not change the sensory discrimination of painful stimuli.

Increase in high frequency EEG activity explains the poor performance of EEG spectral entropy monitor during S-ketamine anesthesia.

OBJECTIVE: To study the effects of S-ketamine on the EEG and to investigate whether spectral entropy of the EEG can be used to assess the depth of hypnosis during S-ketamine anesthesia. METHODS: The effects of sub-anesthetic (159 (21); mean (SD) ng/ml) and anesthetic (1,959 (442) ng/ml) serum concentrations of S-ketamine on state entropy (SE), response entropy (RE) and classical EEG spectral power variables (recorded using the Entropy Module, GE Healthcare, Helsinki, Finland) were studied in 8 healthy males. These EEG data were compared with EEG recordings from 6 matching subjects anesthetized with propofol. RESULTS: The entropy values decreased from the baseline SE 85 (3) and RE 96 (3) to SE 55 (18) and RE 72 (17) during S-ketamine anesthesia but both inter- and intra-individual variation of entropy indices was wide and their specificity to indicate unconsciousness was poor. Propofol induced more pronounced increase in delta power (P<0.02) than S-ketamine, whereas anesthetic S-ketamine induced more high frequency EEG activity in the gamma band (P<0.001). Relative power of 20-70 Hz EEG activity was associated with high SE (P=0.02) and RE (P=0.03) values during S-ketamine anesthesia. CONCLUSIONS: These differences in low and high frequency EEG power bands probably explain why entropy monitor, while adequate for propofol, is not suitable for assessing the depth of S-ketamine anesthesia. SIGNIFICANCE: The entropy monitor is not adequate for monitoring S-ketamine-induced hypnosis.

Clinical application of the blink reflex with stimulation of the mental nerve in lesions of the inferior alveolar nerve.

We evaluated the clinical usefulness of a new modification of the blink reflex (BR) test with electrical stimulation of the innervation area of the mental nerve (MN). We studied the MN BR in 28 patients with traumatic lesions of the inferior alveolar nerve and compared the results with the clinical sensory examination. Within 3 months of the trauma, the MN BR was abnormal in 18 of 20 nerves. In lesions older than 3 months, the test was often normal (in 9 of 11 nerves) despite subjective sensory symptoms and mild clinical signs. Anatomic obstacles to nerve regeneration also gave rise to abnormal MN BR in two patients examined 2 and 4 years after the trauma. The MN BR responses were often absent after violently traumatic lesions, whereas milder injuries commonly produced only latency prolongation of the reflex components. The MN BR is a useful objective method in the diagnosis of sensory loss in the distribution of the MN.

Electrophysiologic evidence for extremely late sensory collateral reinnervation in humans.

We present a patient in whom unexpectedly late sensory recovery occurred over 5 years after removal of a 3-cm piece of the right inferior alveolar nerve (IAN) in tumor surgery of the mandible. For a year after surgery, the distribution of the mental nerve, the terminal branch of the IAN, was totally anesthetic. Thereafter, a gradual subjective sensory recovery occurred centripetally from the surrounding skin distributions. Five years after surgery, findings in electrophysiologic tests were consistent with a total lesion of the right IAN. Two years later, electrophysiologic tests gave, for the first time in humans, objective evidence for sensory collateral sprouting in trigeminal distribution.

Electrophysiological testing of the trigeminofacial system: aid in the diagnosis of atypical facial pain.

The aim of this study was to evaluate the yield of objective electrophysiological testing of the trigeminofacial system in atypical facial pain (AFP). In addition to the clinical neurological examination, two brainstem reflexes covering both the peripheral parts and the central connections of the trigeminal and the facial nerves, the blink and jaw reflexes (BR and JR), were recorded in 17 AFP patients. The control group consisted of 18 healthy volunteers with no history of facial pain or chronic headache. The AFP patients could be divided into three distinct groups on the basis of the clinical and electrophysiological findings. (1) Major trigeminal neuropathy. Four patients had clinical and electrophysiological signs of trigeminal neuropathy (three patients with an afferent pattern of abnormal BR, and one with absent JR on the clinically affected side) despite normal findings in the MRI-scans of the brain. Thus, electrophysiological testing may be more sensitive than MRI in demonstrating pathology in some of the AFP patients. (2) Minor trigeminal neuropathy. Seven patients had signs of increased excitability of the BR in the form of uni- or bilaterally abnormal (diminished or absent) habituation of the R2 component of the BR; two of these patients also showed clinical signs of trigeminal dysfunction, but the MRI-scans were all normal. This deficient habituation of the BR indicates increased excitability of the BR at brainstem level in nearly 50% of our AFP patients. (3) 'Idiopathic', no signs of trigeminal neuropathy. Five patients had normal findings both in the brainstem reflex recordings and in the clinical examinations. Additionally, one patient had abnormal BAEP and EEG recordings. On the group level, the AFP patients had significantly higher thresholds of the tactile R1 component of the BR than the control subjects. Electrophysiological testing may offer a valuable tool for both the clinical evaluation, and the scientific study of AFP.

Recovery of nerve injury after mandibular sagittal split osteotomy. Diagnostic value of clinical and electrophysiologic tests in the follow-up.

The diagnostic value of several clinical, quantitative sensory tests (brush-stroke directional discrimination (BSD), touch detection threshold (TD), warm/cold (W/C) and sharp/blunt discrimination (S/B)), and electrophysiologic tests (mental nerve blink reflex (BR), nerve conduction study (NCS), cold (CDT), and warm (WDT) detection thresholds) in the recovery of inferior alveolar nerve (IAN) injury was evaluated in a prospective 1-year follow-up study of 20 patients after bilateral sagittal split osteotomy (BSSO). The subjective sensory alteration was assessed from patients' drawings. The predictive values of different tests at 2 weeks were determined in relation to the subjective sensory recovery at 12 months. The most pronounced recovery of the nerve damage occurred during the first 3 months according to all measures used. After 3 months, the electrophysiologic tests, especially the NCS, indicated significant further improvement. Except for the TD test, all other clinical test results were normal already at 3 months postoperatively. At early and late controls, the NCS and the thermal quantitative sensory testing could best verify the subjective sensory alteration, and most accurately assess the degree of thick and thin fibre dysfunction. At 1 year, the nerve dysfunction, as revealed by the NCS, corresponded with the figures of sensory alteration reported by the patients (35% R, 40% L). The W/C, BSD, S/B and WDT tests had the best early positive predictive values. Electrophysiologic tests had higher negative predictive values compared to clinical tests.

Risk factors of nerve injury during mandibular sagittal split osteotomy.

There is little objective data about whether surgical technique or mandibular anatomy are a risk for inferior alveolar nerve (IAN) injury during bilateral sagittal split osteotomy (BSSO). Orthodromic sensory nerve action potentials (SNAPs) of the IAN were continuously recorded on both sides in 20 patients with mandibular retrognathia during BSSO operation. Changes in latency, amplitude, and sensory nerve conduction velocity (SNCV) at baseline and at different stages of the operation were analyzed. The SNAP latencies prolonged, the amplitudes diminished, and the SNCVs slowed down during BSSO (P = 0.0000 for all parameters). The most obvious changes occurred during surgical procedures on the medial side of the mandibular ramus. There was a clear tendency towards more disturbed IAN conduction with longer duration of these procedures (right side R = -0.529. P = 0.02; left side R = -0.605, P = 0.006). Exposure or manipulation of the IAN usually had no effect on nerve function, but the IAN conduction tended to be more disturbed in cases with nerve laceration. Low corpus height (R = 0.802, P = 0.001) and the location of the mandibular canal near the inferior border of the mandible (R = 0.52, P = 0.02) may increase the risk of IAN injury. There was no correlation between the age of the patients and the electrophysiological grade of nerve damage.

Intense and recurrent déjà vu experiences related to amantadine and phenylpropanolamine in a healthy male.

We report a case of a 39-year-old caucasian healthy male physician who developed intense and recurrent déjà vu experiences within 24h of initiating concomitant amantadine-phenylpropanolamine treatment against influenza. Déjà vu experiences terminated on discontinuation of medication. Findings in temporal epilepsy suggest that mesial temporal structures, including hippocampus, are related to paramnesic symptoms. On the other hand, previous case reports have confirmed that both amantadine and phenylpropanolamine alone, and particularly in combination, can induce psychotic symptoms due to their dopaminergic activity. The authors suggest that déjà vu experiences may be provoked by increased dopamine activity in mesial temporal structures of the brain.

The mental nerve blink reflex in the diagnosis of lesions of the inferior alveolar nerve following orthognathic surgery of the mandible.

The purpose of this study was to evaluate the diagnostic value of a new modification of the blink reflex test with stimulation of the distribution of the mental nerve in iatrogenic lesions of the inferior alveolar nerve. The test was performed on 23 patients undergoing orthognathic surgery of the mandible, most of them (20) with bilateral sagittal split osteotomies. The function of the inferior alveolar nerve was studied preoperatively, and 2 weeks, 2 months, 6 months and 1 year postoperatively with both mental nerve blink reflex test and clinical neurosensory testing. The objective electrophysiological test proved to be useful in the diagnosis and follow-up of sensory impairment of the inferior alveolar nerve. The results of the mental nerve blink reflex test and clinical neurosensory testing were closely related. The results of the two tests did not differ statistically significantly in the two first postoperative examinations. The positive predictive value of the mental nerve blink reflex test was better than that of clinical neurosensory testing: an initially abnormal reflex response predicted persistent subjective sensory symptoms after one year more reliably than did altered sensation at the first two examinations. Irrespective of the possible coexistent sensory symptoms and signs, a normal mental nerve blink reflex within 2 months after operation also predicted a reasonably good sensory recovery at 1 year.

Assessing the depth of dexmedetomidine-induced sedation with electroencephalogram (EEG)-based spectral entropy.

BACKGROUND: Adequate sedation of critically ill patients improves the outcome of intensive care. Maintaining an optimal level of sedation in the intensive care unit (ICU) is difficult because of a lack of appropriate monitoring methods to guide drug dosing. Dexmedetomidine, a selective alpha(2)-adrenoceptor agonist, has recently been introduced for the sedation of ICU patients. This study investigated the utility of electroencephalogram (EEG)-based spectral entropy monitoring (with M-ENTROPY, GE Healthcare, Helsinki, Finland) for the assessment of dexmedetomidine-induced sedation. METHODS: Eleven healthy, non-smoking men, aged 23.9 +/- 2.5 years (mean +/- standard deviation), were recruited. Spectral entropy was recorded before and during low (0.5 ng/ml) and high (5 ng/ml) plasma concentrations of dexmedetomidine. At the end of the infusion, subjects were awakened by verbal command and light shaking. RESULTS: Spectral entropy decreased from 84 +/- 5 to 66 +/- 16 (P= 0.029) during low dexmedetomidine levels and from 84 +/- 5 to 20 +/- 12 (P < 0.001) during high dexmedetomidine levels. Transitions during loss and regaining of consciousness were analysed separately. Entropy decreased from 76 +/- 8 before to 43 +/- 10 (P < 0.001) after loss of consciousness, and increased from 14 +/- 4 to 63 +/- 13 (P < 0.001) on regaining of consciousness. These changes were consistent across all subjects. Prediction probability and sensitivity values indicated a high predictive performance of the method. CONCLUSION: The depth of dexmedetomidine-induced sedation can be monitored with EEG-based spectral entropy. These results should be confirmed in a clinical setting.

Recovery of somatosensory deficits in acute stroke.

OBJECTIVES: To study the recovery of somatosensory deficits after acute stroke. MATERIAL AND METHODS: A detailed clinical examination of sensation, median nerve somatosensory evoked potentials (SEP), quantitative sensory tests (QST), and subjective evaluation were performed in five acute stroke patients at three control time points up to 12 months after the stroke. RESULTS: The deficit recovered at least partially in all patients, mostly within 3 months after stroke. The improvement in warm and vibration detection thresholds occurred between 3 and 12 months. The SEP improved both by 3 and 12 months. CONCLUSION: The recovery of subjective sensory disturbance occurred in line with the improvement of the clinical sensory tests and QST. The most sensitive measure for somatosensory dysfunction at the early phase was graphesthesia. In our patients, initially normal SEP with a sensory deficit resulted in excellent clinical recovery, whereas initially absent SEP did not necessarily predict poor outcome.

The jaw reflex: maturation in the neonatal period and childhood.

The onset and development of the jaw-reflex responses were studied of 54 neonates and children in up to 15 years of age. Recordings were made with standard EMG equipment. The reflex response was constantly elicited in all but one child of 35 weeks postconceptional age. The latency times showed negative linear correlation with age in the neonatal group and in the children under two years of age. The anatomical basis for the jaw reflex is already established by the 31st fetal week, and the reflex is fully developed by the age of two years. Potential clinical applications of the jaw reflex to child neurology and neonatal intensive care are discussed.

Electrophysiological study of blink reflex in humans: differences in mental and supraorbital nerves.

In order to find an explanation for the discrepancy between previous reports on the consistency of the blink reflex response with stimulation of the mental nerve, the habituation of the blink reflex was studied with stimulation of the supraorbital and mental nerves in 14 healthy adults. A series of eight electrical stimuli was delivered to the distributions of the nerves on each side at frequency rates of 1.0, 0.5, 0.2 and 0.1 Hz. The latencies and peak-to-peak amplitudes of the ipsilateral late blink reflex components (R2i) were measured. The habituation phenomenon was analysed by means of multivariate analysis of the amplitudes, the nerve and frequency effects were determined by means of a repeated measures analysis of variance model. The blink reflex showed more pronounced amplitude attenuation of the consecutive responses with stimulation of the mental than the supraorbital nerve at rates of 0.5 and 0.2 Hz, and marginally so also at 0.1 Hz. For the supraorbital nerve, habituation could be demonstrated with stimulation frequencies of 1.0 and 0.5 Hz, while for the mental nerve a statistically significant habituation phenomenon was found even with the lowest repetition rate of 0.1 Hz. The greater tendency of the mental nerve blink reflex to habituate is obviously one reason why it has previously sometimes been considered too inconsistent to be useful in clinical practice. For the recording of the supraorbital nerve blink reflex, a 10 s interval between stimuli is adequate, whereas longer interstimulus intervals may have to be adopted to obtain consistent blink reflex responses with stimulation of the mental nerve.

Blink reflex with stimulation of the mental nerve. Methodology, reference values, and some clinical vignettes.

INTRODUCTION: In order to develop an objective electrophysiological method for detecting and grading lesions in the inferior alveolar nerve (IAN) and its terminal branch, the mental nerve (MN), the normal physiology of the blink reflex (BR) with stimulation of the distribution of the MN was evaluated and reference values for the MN BR test obtained. MATERIAL AND METHODS: The BR responses to electrical stimulation of the distribution of the MN on each side were recorded in all 44 healthy adults. The onset latencies and peak-to-peak amplitudes were measured and analysed. The effects of the stimulation site, the size of the stimulating electrode, and facilitation by eye closure and mathematical task on the MN BR responses were tested. RESULTS: A small paediatric stimulating electrode was found to be efficient for dermatomal stimulation of the MN distribution. The MN BR responses consisted of an ipsilateral late component (R2i) on the side of the stimulation and a contralateral component (R2c) with similar latency. The latencies were longer and the stimulation thresholds needed to evoke a reflex response were higher with stimulation of the MN, when compared with the BRs with supraorbital nerve stimulation. Eye closure resulted in facilitation of the MN BR in the form of latency shortening, while mathematical task did not have any significant effect on the responses. In addition, the test was found useful in the diagnosis of iatrogenic IAN lesions after extraction of third molars in two patients, and after an orthognathic operation in one patient. CONCLUSION: Contrary to some previous reports, constant MN BR responses can be elicited in healthy adults, which enables further clinical application of this test.

A new technique for recording sensory conduction velocity of the inferior alveolar nerve.

A new electrophysiological technique for recording the sensory conduction velocity (SNCV) of the inferior alveolar nerve (IAN) is described. Bilateral orthodromic recordings were done in 21 healthy adults. The sensory responses of the IAN were obtained in all 42 nerves examined with silver wire or monopolar needle electrodes inserted beneath the zygomatic arc in front of the temporomandibular joint to a depth of 4-4.5 cm, near the oval foramen. A small bipolar surface electrode was used for stimulation at the mental foramen. In 3 subjects, the stimuli were additionally delivered via two monopolar needle electrodes to reduce the stimulus artifact. Single responses were usually sufficient for analysis, but, in some cases, averaging was adopted to improve the signal-to-noise ratio. Response latencies and amplitudes, SNCVs, and interside differences were measured, and the 97.5% upper and 2.5% lower prediction limits calculated for reference limits in clinical practice. This new technique provides a sensitive and objective diagnostic tool for the examination of IAN injuries, and may also be used for intraoperative monitoring of the IAN during mandibular surgery.